Research is focused on elucidating the biochemical events leading to the onset of ocular complications associated with diabetes and galactosemia and their amelioration through the development of appropriate drug therapies. Mechanism(s) by which the enzymes aldose reductase and aldehyde reductase initiate the onset and progression of retinopathy and cataract associated with diabetes and galactosemia are being investigated in a variety of animal models that include galactose-fed dogs and rats. The relationship between aldose reductase, sorbitol dehydrogenase and the amelioration of diabetic complications has been clarified by the use of selected aldose reductase versus sorbitol dehydrogenase inhibitors to demonstrate that aldose reductase inhibition is of primary importance. An intrinsic aldose reductase has been discovered to be present in mammalian tissues and efforts in isolating and characterizing this inhibitor are currently being conducted. Molecular biological techniques are also being utilized to investigate the effectiveness of antisense oligomers in inhibiting aldose reductase. The mechanisms of inhibition and optimization of the design of new aldose reductase inhibitors are being conducted using computer QSAR, quantum mechanical and molecular mechanical techniques. In vivo techniques for non-invasively monitoring the levels of aldose reductase inhibitors in the lens and their efficacy are being developed using molecular resonance imaging and spectroscopic techniques. MRI imaging is being utilized to monitor and characterize osmotic cataract formation in dogs and similar MRI imaging techniques are currently being applied to humans.